Sex-determining region Y (SRY) attributes to gender differences in RANKL expression and incidence of osteoporosis.

ABSTRACT: Receptor activator of nuclear factor κB ligand (RANKL) plays a crucial role in bone metabolism. RANKL gene misregulation has been implicated in several bone and cancer diseases. Here, we aimed to identify novel transcription regulators of RANKL expression. We discovered that transcription factors, sex-determining region Y (SRY) and c-Myb, regulate RANKL expression. We demonstrated that c-Myb increases and male-specific SRY decreases RANKL expression through direct binding to its 5'-proximal promoter. These results are corroborated by the gene expression in human bone samples. In osteoporotic men, expression of RANKL is 17-fold higher, which correlates with the drastically reduced expression (200-fold) of Sry, suggesting that in osteoporotic men, the upregulation of RANKL is caused by a dec

SUBMITTER: Kodric K 

PROVIDER: S-EPMC6802671 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature